Choose mineralocorticoid receptor antagonists over ENaC inhibitors for PA medical therapy
STEP 1 — Gather Information
Confirm diagnosis of primary aldosteronism (PA) and assess if patient is receiving or being considered for PA-specific medical therapy; screen for contraindications to mineralocorticoid receptor antagonists (MRAs) including serum potassium >5.0 mmol/L, eGFR <30 mL/min/1.73m², or pregnancy.
STEP 2 — Rule In / Rule Out
If any MRA contraindication is present (hyperkalemia, advanced renal impairment, pregnancy), rule out MRA therapy and consider epithelial sodium-channel (ENaC) inhibitors as an alternative; otherwise, proceed to evaluate for MRA use.
STEP 3 — Classify or Stratify
Classify the patient as a candidate for MRA therapy when no contraindications exist; stratify further by hypertension severity and need for potassium monitoring to guide initial MRA dosing.
STEP 4 — Decide
For candidates without contraindications, initiate an MRA (prefer spironolactone for its lower cost and greater availability); if contraindications preclude MRA use, consider an ENaC inhibitor (amiloride or triamterene) after confirming lack of MRA-specific contraindications.
Clinical Guardrails / Mimics / Pitfalls
Do not use ENaC inhibitors as first-line when MRAs are tolerated; avoid MRAs in hyperkalemia, severe renal impairment, or pregnancy; do not initiate therapy without baseline potassium and renal function; do not up-titrate MRAs without monitoring for gynecomastia or menstrual irregularities; do not ignore dietary sodium intake, as high salt blunts MRA response.
Concrete Clinical Example
A 58-year-old hypertensive patient with confirmed PA (ARR >40, suppressed renin) and normal potassium (4.2 mmol/L) and eGFR 68 mL/min/1.73m² is evaluated for medical therapy; no MRA contraindications are present, so spironolactone 25 mg daily is started with plans to titrate based on BP and renin response.
Source: Primary Aldosteronism: An Endocrine Society Clinical Practice Guideline, Endocrine Society, 2025, https://doi.org/10.1210/clinem/dgaf284